Prefunctionalised PLGA microparticles with dimethylaminoethyl moieties promote surface cell adhesion at physiological condition
Prefunctionalised PLGA microparticles with dimethylaminoethyl moieties promote surface cell adhesion at physiological condition
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DOI：
10.1016/j.eurpolymj.2021.110466
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发表时间：
2021-04
影响因子：
6
通讯作者：
Noelia D. Falcon;A. Saeed
中科院分区：
文献类型：
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作者：
Noelia D. Falcon;A. Saeed
合成的可水解降解聚酯已广泛应用于各种临床和生物医学环境;用作细胞培养系统、药物递送系统、组织修复支架和医疗器械。这一成功部分归功于其生物相容性和可调降解特性。然而，粘合部分的缺乏限制了聚酯与多孔材料相互作用的能力，因此阻碍了它们在这些应用中的有效性。已经开发了几种物理和化学后修饰技术来插入粘附部分;然而，这些方法的性质对于转化医学来说仍然是复杂和麻烦的。为了克服这一缺陷，我们提出了一种新的预功能化方法，用于生成具有集成粘附部分的聚（乳酸-羟基乙酸共聚物）PLGA微粒作为原理证明。该策略在生理条件下促进表面细胞粘附，而不需要进一步的后修饰。预官能化方法的基础是在标准本体开环聚合方法中利用2-2-二甲基氨基乙醇作为引发剂以获得PLGADMAE聚合物。所得聚合物随后通过膜乳液用于制造微粒。该方法允许控制微粒的形态和尺寸分布。通过与脂肪源性干细胞共培养，研究了新型PLGADMAE微粒的表面细胞粘附特性。扫描电子显微镜显示，新的PLGADMAE微粒在生理条件下容易促进ADSC的粘附。LDH和LIVE/DEAD测定表明，与未修饰的PLGA微粒相比，表面官能化的PLGADMAE微粒保持低毒性。热重和差示扫描量热分析证实，与对照PLGA相比，聚合物的本体性质保持不变。凝胶渗透色谱和扫描电子显微镜成像表明，新的PLGADMAE的降解曲线相比，标准的PLGA聚合物增强。这种新的预功能化策略消除了对后修饰的需要，并且可以快速发展以开发具有增强的细胞粘附和可调表面化学的可生物降解的生物材料，以允许更好地控制和/或维持与活细胞和组织的相互作用。这种新方法的意义将在细胞递送、细胞扩增、组织工程和再生医学领域产生深远影响。
Synthetic hydrolytically degradable polyesters have seen widespread translation into a variety of clinical and biomedical settings; finding use as cell culture systems, drug delivery systems, tissue repair scaffolds, and medical devices. This success is owed in part due to their biocompatible nature and tuneable degradation profile. However, the lack of adhesion moieties limits the capacity of the polyesters to interact with cellular material and as such hampers their effectiveness within these applications. Several physical and chemical post-modification techniques have been developed to insert adhesion moieties; however, the nature of these methods remains complex and troublesome for translational medicine. To combat this flaw, we present a novel prefunctionalization method for the generation of poly (lactic-co-glycolic acid) PLGA microparticles with integrated adhesion moieties as a proof-of-principle. This strategy promotes surface cell adhesion at physiological conditions without the requirement for further post-modification. The basis of the prefunctionalization method was to utilise the 2-2-dimethylaminoethanol as an initiator in a standard bulk Ring Opening Polymerization process to obtain PLGADMAEpolymers. The resultant polymers were subsequently used in the fabrication of the microparticles, via membrane emulsion. This process allowed control over the morphology and size distribution of the microparticles. The surface cell adhesive properties of the new PLGADMAEmicroparticles were investigated via co-culture with Adipose-Derived Stem Cells. Scanning Electron Microscopy showed that the new PLGADMAEmicroparticles readily promote adhesion of the ADSCs at physiological conditions. LDH and LIVE/DEAD assays demonstrated that the surface functionalised PLGADMAEmicroparticles maintained a low toxicity profile compared to the unmodified PLGA microparticles. Both thermogravimetric and differential scanning calorimetric analysis confirmed that the bulk properties of the polymer remained unchanged compared to the control PLGA. Gel Permeation Chromatography and Scanning Electron Microscopy imaging showed that the degradation profile of the new PLGADMAEwas enhanced compared to that of standard PLGA polymers. This novel prefunctionalization strategy eliminates the need for post-modification and could evolve rapidly to develop biodegradable biomaterials with enhanced cell adhesion and tuneable surface chemistry to allow greater control and/or maintain interaction with living cells and tissues. The implication of this new approach would be far reaching in the field of cell delivery, cell expansion, tissue engineering and regenerative medicine.